title: Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study.
abstract: OBJECTIVE
  Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm.
  
  
  OBJECTIVE
  To define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52,298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine.
  
  
  METHODS
  The median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy.
  
  
  RESULTS
  Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had increased odds of developing a suppressed thyrotropin level, whereas individuals with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus, hypertension, and raised lipid levels) did not.
  
  
  CONCLUSIONS
  We observed a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism and a substantial risk of developing a suppressed thyrotropin level following therapy. Large-scale prospective studies are required to assess the risk-benefit ratio of current practice.
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom2Department of Social and Community Based Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Taylor
authors.affiliation: Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, University of Bristol, Bristol, United Kingdom.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Minassian
authors.affiliation: Department of Social and Community Based Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Sayers
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Mohd S
authors.initials: MS
authors.lastname: Draman
authors.affiliation: University Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Greenwood
authors.affiliation: University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Hamilton
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Onyebuchi
authors.initials: O
authors.lastname: Okosieme
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors.forename: Vijay
authors.initials: V
authors.lastname: Panicker
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Thomas
authors.affiliation: Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom3Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, University of Bristol, Bristol, United Ki.
authors.forename: Colin
authors.initials: C
authors.lastname: Dayan
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004358:Drug Therapy / Q000639:trends; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D013972:Thyrotropin; D013974:Thyroxine